Our research has been concerned primarily with the application of high resolution electron microscopy, cytochemical, and immunochemical methods to the study of pathogenic fungi. Selected strains of Histoplasma capsulatum, Cryptococcus neoformans, Blastomyces dermatidis, Torulopsis glabrata, Candida spp. and Aspergillus fumigatus have been used. In addition, nonpathogenic fungi, certain algae, and a few actinomycetes have been investigated when they appeared pertinent to the purpose of our project. Objectives are: (1) Visualization of macromolecular structures and morphological variations of cellular components during physiological processes, such as cell division including budding and septation, as well as variations in ribosomes, glycogen particles, and lipid droplets; changes in number and features of nuclei, mitochondria and other cell organelles during transition from yeast to hyphal growth and vice versa. (2) Morphogenetic observations on dormant and germinating spores, particularly conidia of A. fumigatus, chlamydospores of C. albicans, and tuberculate spores of H. capsulatum. (3) Comparison of growth characteristics of dimorphic fungi, under in vitro conditions cultured saprophytically at room temperature or under parasitic conditions in infected animals. Special attention is given to significant ultrastructural changes during transition from the mycelial to the yeastlike phase, i.e., from saprophytic to parasitic conditions. (4) Characterization of host-fungus interrelationships (phagocytosis and lysosomal enzymes). (5) Search for evolutionary trends among the selected organisms, many of which are ranked in doubtful taxonomic positions. Possible relationship is also sought between fungi and more primitive microorganisms, such as procaryotic algae (e.g., Synechococcus), as well as some advanced eucaryotic algae (e.g., heterotrophic Cyanidium). The project is concerned with the relationship of form to function at the molecular level. It concentrates on microorganisms of significance in disease, but also involves nonpathogenic organisms which may privide basic information on evolutionary trends from lower to higher forms of life.